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Toxicological information

Toxicity to reproduction

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Administrative data

fertility, other
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data contained in EU risk assessment report of the substance - credibility is assumed. Reference to origin (Hoechst)

Data source

Referenceopen allclose all

Reference Type:
other: EU risk assessment report
No information
Federal Institute for Occupational Safety and Health, Division for Chemicals and Biocides Regulation, Germany
Bibliographic source:
European Union Risk Assessment Report, 4-tert-butylbenzoic acid, CAS No: 98-73-7, EINECS No: 202-696-3, Toxicity for reproduction, p. 68-75, Final Approved Version, July 2009
Reference Type:
study report

Materials and methods

Principles of method if other than guideline:
Male rats were exposed to the test substance and mated with non-exposed females. The effect of the test substance on various endpoints was examined: length of gestation, numbers of live and dead borns, sex, weight and any externally visible anomalies of the new-borns, etc.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
4-tert-butylbenzoic acid
EC Number:
EC Name:
4-tert-butylbenzoic acid
Cas Number:
Molecular formula:
4-tert-butylbenzoic acid

Test animals


Administration / exposure

Route of administration:
oral: feed

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Lower dietary levels of 20 and 100 ppm PTBBA did not result in any weight gain impairment of the animals. At the 500 ppm level reversible reduction in body weight was observed in treated animals. Males gained less body weight during the exposure period resulting in body weights 14 % lower in comparison to the controls after 70 days of exposure, yet continued to develop normally after the animals had changed to their usual diet. Ten males of the 20 ppm exposed group and 9 males of the 100 ppm exposed group revealed to be fertile during the first mating trial (Table 1). Eight males of the 20 ppm group, 7 males of the 100 ppm group and 9 males of the control group impregnated both of the two females. One male of the 100 ppm group was not successful in impregnating but sired one of its females. No pregnancies were produced during the first mating interval from males exposed to dietary levels of 500 ppm. Three males inseminated one female each; however, no pregnancies resulted, whereas from the other 7 males no sperm was detected in vaginal smears of their female partners.

During the second mating trial 70 days after the end of the treatment period the recovery group males revealed all to be fertile (Table 2). Eight males of the former 500 ppm group impregnated both of their female partners, while two males of this group and one male of the former 100 ppm group impregnated only one female partner each.

No treatment-related effects were observed for duration of the gestational period and on parturition. There were no differences in the numbers of live borns per litter, in sex ratio and in mean body weights of the new-borns between the controls and the treatment groups. No externally visible anomalies in new-borns were recorded. In the parental males organ weights for brain, heart, liver, spleen and kidneys of the treated groups did not differ from those of the controls. Also testes weights in the 20 and 100 ppm group did not differ from those of the controls. In males of the 500 ppm group however, after recovery for more than 70 days, mean testes weights were reduced (2.76 g) in comparison to that of the controls (3.14 g). Histopathological evaluation of the male reproductive organs did not reveal any differences in comparison to the controls for animals exposed to the 20 and 100 ppm level. For animals exposed to the 500 ppm level minor lesions at the germinative epithelium were found which were confined to few tubules only. No histopathological changes were found for the 500 ppm group for prostate, seminal vesicles and epididymides and its sperm. A NOAEL/male fertility of 20 ppm (according to 1.6 mg PTBBA/kg bw/d) can be derived from the study based on the finding of infertility/inability to impregnate at dietary dosages of 100 ppm (according to 7.9 mg PTBBA/kg bw/d). No data on possible female fertility impairment or other functional studies could be identified in the available database.

Table 1: Outcome of the 1st mating trial

1. Mating trial Controls Treatment groups
20 ppm 100 ppm 500 ppm
Males investigated (n) 10 10 10 10
Fertile males
[successful in
impregnation] (n)
10 10 9 0
Female partners
investigated (n)
20 20 20 20
Females sperm
positive /pregnant
19 18 6 0
Females sperm
positive /nonpregnant
0 0 2 3
Females neither
sperm positive nor
1 2 2 17

Table 2: Outcome of the 2nd mating trial

2. Mating trial Recovery groups
100 ppm 500 ppm
Males investigated (n) 1 10
Fertile males
[successful in
impregnation] (n)
1 10
Female partners
investigated (n)
2 20
Females sperm
positive /pregnant
1 18
Females sperm
positive /nonpregnant
1 1
Females neither
sperm positive nor
0 1

Applicant's summary and conclusion

According to the results on male rats fertility a NOAEL of 20 ppm of the test substance, corresponding to 1.6 mg PTBBA/kg bw/d, was derived.